Herbicidally active phenoxyalkanecarboxylic acid derivatives

ABSTRACT

A compound of the formula: ##STR1## wherein Q 1  is CH or N; R is H or C 1  -C 5  alkyl; X is H, halogen, CF 3 , or NO 2  ; Y is H or halogen; Z is --O-- or --NH--; A is ##STR2## wherein Q 2 , and Q 3  are each CH or N; R 1  and R 2  are each H, C 1  -C 5  alkyl, C 1  -C 5  alkoxy, or C 2  -C 6  alkxoycarobnyl; R 3 , R 4 , and R 5  are each H or C 1  -C 5  alkyl; R 6  is H, halogen, or C 1  -C 5   alkyl; R 7 , R 8 , R 9 , and R 10  are each H or C 1  -C 5  alkyl; R 11  is H, C 1  -C 5  alkyl, C 1  -C 5  alkoxy, C 2  -C 6  alkenyl, C 6  -C 10  aryl, C 7  -C 15  aryloxyalkyl, or C 7  -C 15  aralkyl; R 12  and R 13  are each H or C 1  -C 5  alkyl; R 14  is C 1  -C 5  alkyl, C 2  -C 6  alkenyl, C 5  -C 10  aryl, or C 7  -C 15  aralkyl; or R 13  and R 14  taken together form C 3  -C 4  alkylene, V 1  and V 2  are each H, halogen, NO 2 , CN, or CF 3  ; V 3  is halogen or CF 3  ; W 1  is --O-- or --NH--; W 2  is --(CH 2 ) n  -- wherein n is 0 or 1, or CO; X 1  is halogen, or a salt thereof, which is effective as a herbicidal agent.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to novel herbicidally active compounds(i.e., phenoaxyalkanecarboxylic acid derivatives) having the formula:##STR3## wherein Q¹ is CH or N; R is H or C₁ -C₅ alkyl; X is H, halogen,CF₃, or NO₂ ; Y is H or halogen; Z is --O-- or --NH--; A is ##STR4##wherein Q² and Q³ are each CH or N; R¹ and R² are each H, C₁ -C₅ alkyl,C₁ -C₅ alkoxy, or C₂ -C₆ alkoxycarbonyl; R³, R⁴ and R⁵ are each H or C₁-C₅ alkyl; R⁶ is H, halogen, or C₁ -C₅ alkyl; R⁷, R⁸, R⁹, and R¹⁰ areeach H or C₁ -C₅ alkyl; R¹¹ is H, C₁ -C₅ alkyl, C₁ -C₅ alkoxy, C₂ -C₆alkenyl C₆ -C₁₀ aryl, C₇ -C₁₅ aryloxyalkyl, or C₇ -C₁₅ aralkyl; R¹² andR¹³ are each H or C₁ -C₅ alkyl; R¹⁴ is C₁ -C₅ alkyl, C₂ -C₆ alkenyl, C₆-C₁₀ aryl, or C₇ -C₁₅ aralkyl; or R¹³ and R¹⁴ taken together form C₃ -C₄alkylene; V¹ and V² are each H, halogen, NO₂, CN, or CF₃ ; V³ is halogenor CF₃ ; W¹ is --O-- or --NH--; W² is --(CH₂)_(n) -- wherein n is 0 or1, or --CO--; and X¹ is halogen; or a salt thereof.

These compounds (I) are useful as an effective ingredient for herbicides

2. Description of the Related Art

A series of α-(p-phenoxyphenoxy)propionic acid type andα-(p-pyridyloxyphenoxy)propionic acid type compounds have been developedas important herbicides in agriculture and horticulture. Theseα-(p-phenoxyphenoxy)propionic acid type andα-(p-pyridyloxyphenoxy)propionic acid type herbicides are safe in thatthey have little influence on useful plants to be harvested, comparedwith the phenoxy type herbicides formerly employed, and that they have astronger herbicidal activity. But, these α-(p-phenoxyphenoxy)propionicacid type and α-(p-pyridyloxyphenoxy)propionic acid type herbicides havea lower selectivity for plants of the rice family, causing drug damageto, for example, rice, wheat, and barley which are useful plants, andexhibit no effect on some perennial weeds, and therefore, they areextremely limited in, for example, application time and applicationmethods.

SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to provide a novelcompound (i.e., a phenoaxyalkanecarboxylic acid derivatives) having aherbicidal activity, which is a herbicide which will not cause drugdamage to rice, wheat or barley, and having a high selectivity betweenthe plants of the rice family, while maintaining the characteristics ofthe above-mentioned α-(p-phenoxyphenoxy)propionic acid type orα-(p-pyridyloxyphenoxy)propionic acid type herbicides, and a herbicidecontaining the phenoaxyalkanecarboxylic acid derivative.

Other objects and advantages of the present invention will be apparentfrom the following description.

In accordance with the present invention, there is provided a compoundhaving the above-mentioned formula (I), or a salt thereof.

In accordance with the present invention, there is also provided aherbicide containing, as an effective ingredient, a herbicidallyeffective amount of a compound having the above-mentioned formula (I).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present inventors, while studying the development of a herbicide notcausing drug damage to rice, wheat, or barley and with an enhancedselectivity between monocotyledon plants, while maintaining thecharacteristics of these pyridyloxyphenoxy type herbicides, found aherbicidally active compound having the above-mentioned general formula(I), or a salt with thereof, with an extremely potent activity and goodselectivity.

Examples of the above-mentioned salts are those of an inorganic acidsuch as hydrochloric acid, sulfuric acid, nitric acid, or phosphoricacid and those of an organic acid such as p-toluenesulfonic acid ormethane sulfonic acid.

In the above-mentioned formula (I), when the substituent A is ##STR5##the resultant compound is an α-phenoxyalkanecarboxylic acid derivativehaving the formula: ##STR6##

In the formula (1-1), wherein X is H, Cl, NO₂ and CF₃, and the halogenatom of the substituents Y, V¹ and V² may include, for example,fluorine, chlorine, bromine.

Examples of the lower alkyl group of R are methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, tert-butyl, and n-pentyl.

The present compound is different from the herbicides well known in theart, in that it contains an α-phenoxyalkanecarboxylic acid and ap-substituted phenol or a p-substituted aniline in the skelton thereof,and therefore, has a very low toxicity to the human body.

The α-phenoxyalkanecarboxylic acid derivative having the above formula(1-1) can be prepared according to the process as described below.

Thus, the α-phenoxyalkanecarboxylic acid derivative according to thepresent invention represented by the formula (1-1) can be obtained athigh yield by allowing a carboxylic acid or a carboxylic acid derivativehaving the formula (2a-1): ##STR7## wherein Z¹ represents hydroxy group,a halogen atom or an active ester group, to react with a p-substitutedphenol or p-substituted aniline of the formula (3-1): ##STR8## whereinZ² represents an oxygen atom or NH in the presence or absence of a base.

Examples of the suitable base are an alkali hydroxide or atrialkylamine.

The reaction conditions for the above reaction are not particularlylimited, and the reaction can proceed in water or an organic solvent atroom temperature or lower for 1 to 12 hours.

The compound of the present invention obtained as described above can bepurified after completion of the reaction according to generalpurification methods.

Examples of these general purification methods includerecrystallization, column chromatography, and thin layer chromatography.

In the above-mentioned formula (I), when the substituent A is ##STR9##the resultant compound is an acylaminobenzenesulfonamide derivativehaving the formula: ##STR10##

In the formula (1-2), wherein X is Cl and CF₃, and the halogen atom ofthe substituents Y may include fluorine, chlorine, and bromine.

Examples of the lower alkyl group R, R¹, and R² are methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, and the like.

Examples of the lower alkoxy group of R¹ and R² include methoxy, ethoxy,n-propoxy, isoproxy, n-butoxy, isobutoxy, and the like.

Examples of the lower alkoxycarbonyl group of R¹ and R² includemethoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl,and the like.

The compound of the present invention is different from the herbicideswell known in the art in that it contains an α-phenoxyalkanecarboxylicacid and aminobenzenesulfonamide in the skelton thereof, and therefore,has a very low toxicity to the human body.

The acylaminobenzenesulfonamide derivative having the above formula(1-2) can be prepared according to the process as described below.

Thus, the acylaminobenzenesulfonamide derivative according to thepresent invention represented by the formula (1-2) can be obtained athigh yield by allowing a carboxylic acid or a carboxylic acid derivativehaving the formula (2a-1): ##STR11## wherein Z¹ represents hydroxygroup, a halogen atom or an active ester group, to react with ap-substituted phenol or p-substituted aniline of the formula (3-2):##STR12## in the presence or absence of a base.

As the suitable base, for example, an alkali hydroxide or atrialkylamine can be used.

The reaction conditions for the above reaction are not particularlylimited, and the reaction can proceed in water or an organic solvent atroom temperature or lower for 1 to 12 hours.

The compound of the present invention obtained as described above can bepurified after completion of the reaction according to generalpurification methods.

Examples of these general purification methods includerecrystallization, column chromatography, and preparative thin layerchromatography.

In the above-mentioned formula (I), when the substituent A is ##STR13##the resultant compound is an o-haloketone derivative having the formula(1-3): ##STR14## wherein X is CF₃, X¹ may include a fluorine, chlorine,bromine, or iodine. Representative of the lower alkyl group of thegroups R³, R⁴, R⁵ and R⁶ are methyl, ethyl, n-propyl and isopropyl.Examples of the halogen atom of the group R⁶ may include a fluorine,chlorine, bromine or iodine, and the lower alkyl group are representedby methyl, ethyl, n-propyl, and isopropyl groups.

The α-haloketone derivative represented by the above-mentioned formula(1-3) according to the present invention can be prepared according tothe processes described below.

Preparation process 3-A

This process comprises allowing an amine salt of a compound having theformula (2-3): ##STR15## to react with a compound represented by theformula (3-3): ##STR16## wherein Z³ represents a halogen atom, R³ and R⁴may be either identical or different and each represent a hydrogen atomor a lower alkyl group, and subsequently treating the compound formed ofthe formula (4-3): ##STR17## with a hydrogen halide or an aqueoushydrogen halide solution.

Preparation process 3-B

This process comprises allowing an amine salt of a compound having theabove-mentioned formula (2-3) to react with a compound represented bythe formula (5-3): ##STR18## wherein Z³ represents a halogen atom, R³,R⁴, and R⁵ each independently represent a hydrogen atom or a C₁ -C₅lower alkyl group, R⁶ represents hydrogen atom, a halogen atom or a C₁-C₅ lower alkyl group in a non-protonic polar solvent.

Preparation process C

This process comprises activating the carboxyl group of a compoundhaving the formula (6-3): ##STR19## according to the acid halide method,the mixed acid anhydride method or the active esterification method,then allowing the activated compound to react with diazomethane, andsubsequently, treating the reaction product with a hydrogen halide or anaqueous hydrogen halide solution.

As the amine to be used in the above preparation process A and thepreparation process B, there may be included dialkylamines andtrialkylamines, in general, but preferably dicyclohexylamine is used.

The non-protonic polar solvent in the preparation process A and thepreparation process B is not particularly limited, but preferableexamples include dimethylformamide and dimethylsulfoxide.

The condensation reactions of the above-mentioned preparation processesA and B may be generally conducted at a temperature of 0° C. to 100° C.,preferably room temperature to 60° C. On the other hand, thehalogenation reaction in the above preparation processes A and C isgenerally conducted at -20° C. to 40° C., preferably at 0° C. to roomtemperature. Further, the temperature for carrying out thediazomethylation reaction in the above preparation process C may begenerally -20° C. to 30° C., preferably 0° C. to 5° C.

The reaction is generally completed within 0.1 to 3 hours.

The compound of the present invention obtained as described above can bepurified by general purification methods, if desired. Examples of thesegeneral purification methods may include recrystallization, columnchromatography, and thin layer chromatography.

In the compounds according to the present invention, optical isomersbased on R, R³, R⁴, R⁵, R⁶ and X¹ exist, and all of these are alsoincluded within the scope of the present invention.

In the above-mentioned formula (I), when the substituent A is ##STR20##the resultant compound is an α-substituted ketone derivative having theformula (1-4): ##STR21##

In the above formula (1-4), representative of the lower alkyl groupsrepresented by the groups R⁷, R⁸, R⁹, and R¹⁰, are alkyl groups having 1to 5 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl,and isobutyl groups, and representative examples of the lower alkylgroup represented by R¹¹ include alkyl groups having 1 to 5 carbon atomssuch as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, andtert-butyl, or halo-substituted alkyl groups such as chloroethyl,chloropropyl, bromoethyl, bromopropyl, trifluoromethyl, andtrifluoroethyl groups. Representative of the lower alkoxy group arealkoxy groups having 1 to 5 carbon atoms such as methoxy, ethoxy,n-propyloxy, and tert-butoxy groups; representative of the lower alkenylgroup are alkenyl groups having 2 to 4 carbon atoms, such as vinyl,allyl groups, or substituted alkenyl groups substituted with halogens;representative of the aryl group are aryl groups having 6 to 10 carbonatoms, such as phenyl, p-chlorophenyl, and tolyl groups, and substitutedderivatives thereof substituted with halogens; representative of thearyloxyalkyl group are aryloxyalkyl groups having 7 to 10 carbon atoms,such as phenoxymethyl and p-chlorophenoxyethyl groups and substitutedderivatives thereof substituted with halogens; and representative of thearalkyl group are aralkyl groups having 7 to 10 carbon atoms, such asphenethyl and phenylpropyl groups and substituted derivatives thereofsubstituted with halogens.

The compound of the above formula (1-4) according to the presentinvention is different from the herbicides well known in the art in thatit contains pyridyloxyphenoxypropionic acid and an α-substituted ketonederivative in the skelton thereof, and has an extremely low toxicity tothe human body.

The α-substituted ketone derivative having the above-mentioned formula(1-4) of the present invention can be prepared as described below.

Preparation process 4-A

An amine salt of a compound of the formula: ##STR22## is allowed toreact with a compound of the formula: ##STR23## wherein Z⁴ represents achlorine atom or bromine atom, W¹ represents an oxygen atom or iminogroup, W² represents a single bond or carbonyl group, R¹¹ represents ahydrogen atom, a lower alkyl group, a lower alkoxy group, a loweralkenyl group, an aryloxyaralkyl group or an aralkyl group, which may beeach substituted in a non-protonic polar solvent.

Preparation process 4-B

An amine salt of a compound of the formula (2-4) is allowed to reactwith a compound of the formula (4-4): ##STR24## wherein Z⁵ and Z⁶ may beidentical or different, and represent a chlorine atom or bromine atom,and R⁷ R⁸, R⁹, and are as defined above in a non-protonic polar solventto derive a compound of the formula: ##STR25## and subsequently, thisreaction product is allowed to react with an amine salt of a carboxylicacid having the formula:

    R.sup.11 --COOH                                            (4-6)

(wherein R¹¹ is as defined above) in a non-protonic polar solvent.

As the amine to be used in the above-mentioned preparation process 4-Aand the preparation process 4-B, there may be included dialkylamines,trialkylamines, in general, but preferably dicyclohexylamine is used.

The non-protonic polar solvent in the preparation process 4-A and thepreparation process 4-B is not particularly limited, but preferableexamples include dimethylformamide, dimethylsulfoxide. The condensationreactions of the above preparation process 4-A and the preparationprocess 4-B may be generally conducted at a temperature of 0° C. to 100°C., preferably room temperature to 60° C. The reaction is generallycompleted within 0.1 to 3 hours.

The compound (1-4) of the present invention obtained as described abovecan be purified by general purification methods, if desired. Examples ofthese general purification methods include recrystallization, columnchromatography, and thin layer chromatography.

In the compounds according to the present invention, optical isomersbased on the above substituents R⁷, R⁸, R⁹, R¹⁰, and W¹ andpyridyloxyphenoxypropionic acid exist, and all of these are alsoincluded within the scope of the present invention.

The compounds of the present invention thus obtained have a low toxicityto the human body and domestic animals, and have an extremely specificand potent growth controlling activity for monocotiledon plants. Thissuggests that the compounds of the present invention can be widely usedas herbicides.

In the formula (I), when the substituent A is ##STR26## the resultantcompound is a phenoxyalkane carboxylic acid derivative having theformula (1-5): ##STR27##

In the formula (1-5), examples of the alkyl group R are methyl, ethyl,n-propyl, and isopropyl, and the halogen atom of V³ is chlorine,bromine, fluorine, or iodine.

The present compound is different from the herbicides well known in theart in that it contains a phenoxyalkanecarboxylic acid and nitrophenolor nitroaniline in the skelton thereof, and therefore, has a very lowtoxicity to the human body.

The phenoxyalkanecarboxylic acid derivative having the above formula(1-5) can be prepared according to the process as described below.

Thus, the phenoxyalkanecarboxylic acid derivative according to thepresent invention having the formula (1-5) can be obtained at a highyield by allowing a carboxylic acid or a carboxylic acid derivativehaving the formula (2a-5) or (2b-5): ##STR28## wherein Z⁵ representshydroxyl, halogen, or an active ester group, to react with nitrophenolor nitroaniline having the formula (3-5): ##STR29## in the presence orabsence of a base.

As the suitable base, for example, an alkali hydroxide or an organicamine such as a trialkylamine or pyridine can be used.

The reaction conditions for the above reaction are not particularlylimited, and the reaction can proceed in water or an organic solvent atroom temperature or lower for 1 to 12 hours.

The present compound obtained as described above can be purified aftercompletion of the reaction according to general purification methods.

Examples of these general purification methods includerecrystallization, column chromatography, and thin layer chromatography.

In the compounds according to the present invention, optical isomersbased on the one asymmetric carbon atom exist, and all of these are alsoincluded within the scope of the present invention.

The present compounds thus obtained have a low toxicity to the humanbody and domestic animals, and have an extremely specific and potentgrowth controlling activity for monocotiledon plants. This suggests thatthe compounds of the present invention can be widely used as herbicides.

In the formula (I), when the substituent A is ##STR30## the resultantcompound is an α-substituted ketone derivative having the formula (1-6):##STR31##

The α-substituted ketone derivative having the above-mentioned formula(1-6) according to the present invention can be prepared according tothe processes as described below.

Thus, the α-substituted ketone derivative according to the presentinvention having the formula (1-6) can be obtained by allowing an aminesalt of a compound having the formula (2-6): ##STR32## to react with acompound having the formula (3-6): ##STR33## wherein Z⁶ representshalogen.

Examples of the amines usable in the above reaction are dialkylaminesand trialkylamines, but preferably, dicyclohexylamine is used. Thereaction is usually carried out in an aprotic solvent. Examples of suchsolvents are dimethylformamide and dimethylsulfoxide. The reactiontemperature is generally 0° C. to 100° C., preferably room temperatureto 60° C. The reaction is generally completed in 0.1 to 3 hours.

The present compound obtained as described above can be purified aftercompletion of the reaction according to general purification methods.

Examples of these general purification methods includerecrystallization, column chromatography, and thin layer chromatography.

In the compounds according to the present invention, optical isomersbased on the two asymmetric carbon atoms exist, and all of these arealso included within the scope of the present invention.

The present compounds thus obtained have a low toxicity to the humanbody and domestic animals, and have an extremely specific and potentgrowth controlling activity for monocotiledon plants. This suggests thatthe compounds of the present invention can be widely used as herbicides.

The compounds of the present invention as the herbicide can be generallyapplied while mixed with suitable carriers, for example, solid carrierssuch as clay, diatomaceous earth, or liquid carriers such as water,alcohols, aromatic hydrocarbons, ethers, ketones, and esters. Also, ifdesired, they can be provided in a form such as an emulsion, wettableagent, powder, granule, may be added with an emulsifier, dispersingagent, suspending agent, spreading agent, stabilizer, and may be appliedas a mixture with various kinds of herbicides, various pesticides,germicides, plant growth controllers.

In the practice of the present invention, the concentration of thecompound of the present invention can be widely varied, but preferablyis in the range of 0.5 to 10 g per 10 ares. The various preparationsdescribed above can be prepared so as to contain 0.5% to 90% by weightof the active ingredient.

EXAMPLES

The present invention now will be further illustrated by, but is by nomeans limited to, the following Reference Examples, Synthesis Examples,and Test Examples.

REFERENCE EXAMPLE 1: SYNTHESIS OF THE STARTING MATERIAL HAVING THEFORMULA (2a-1) (A) 2-(4-(4-Chlorophenoxy)phenoxy)propionic acidchloride:

4-Bromochlorobenzene (3.8 g), hydroquinone monomethyl ether (3.1 g) andpotassium hydroxide (1.5 g) and copper powder (0.1 g) were mixed and thereaction was carried out at 160° C. to 200° C. for 3 hours. Aftercooling to room temperature, the reaction mixture was extracted withbenzene (100 ml) and washed with 1N sodium hydroxide, water, andsaturated aqueous sodium chloride. After drying over anhydrous magnesiumsulfate, the solvent was evaporated under a reduced pressure and theresidue was purified by medium pressure column chromatography usingsilica gel, to obtain 4-(4-chlorophenoxy)phenol methyl ether (2.5 g).

The methyl ether obtained (2.5 g) was dissolved in dry methylenechloride (20 ml), the solution was added to a solution of borontribromide (3.0 g) in dry methylene chloride (20 ml), and the mixturewas stirred at room temperature for 2 hours. After an addition of water,the mixture was extracted with ether (100 ml) and the extract was driedover anhydrous magnesium sulfate, followed by evaporation of the solventto obtain 4-(4-chlorophenoxy)phenol (2.4 g).

The phenol obtained (1.8 g) and sodium hydroxide (0.7 g) were dissolvedin water (10 ml), and the solution was heated after an addition of2-bromopropionic acid (1.2 g), and then evaporated to dryness. Theresidue was dissolved in water (20 ml), washed with ether (20 ml), thenmade acidic with an addition of 1N hydrochloric acid and extracted withether (50 ml). The extract was dried over anhydrous magnesium, and thesolvent was evaporated under a reduced pressure to obtain2-(4-(4-chlorophenoxy)propionic acid (1.1 g) (m.p. 115° C.-117° C.).

The carboxylic acid (0.9 g) was dissolved in dry benzene (10 ml) andrefluxed, after an addition of thionyl chloride (5 ml), for 2 hours. Thesolvent and thionyl chloride were than evaporated under a reducedpressure to obtain 2-(4-(chlorophenoxy)phenoxy)propionic acid chloride(1.0 g).

(a) 2-bromoacetic acid, (b) 2-bromobutyric acid, and (c) 2-bromovalericacid in the above (A), were used to obtain (a'),4-(4-chlorophenoxy)phenoxyacetic acid chloride, (b')2-(4-(4-chlorophenoxy)phenoxybutyric acid chloride, (c')2-(4-(4-chlorophenoxy)phenoxy)valeric acid chloride, respectively. Also,by using (d) 4-bromonitrobenzene instead of 4-bromochlorobenzene in theabove (a), (d') 2-(4-(4-nitrophenoxy)phenoxy)propionic acid chloride wasobtained.

Also, by using a commercially available 4-phenoxyphenol instead of4-(4-chlorophenoxy)phenol, 2-(4-phenoxyphenoxy)propionic acid chloridewas obtained.

(B) 2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxypropionic acidchloride hydrochloride:

Ethyl 2-bromopropionate (36.2 g) and hydroquinone monobenzyl ether (40.0g) were dissolved in dry dimethyl sulfoxide (100 ml), and pulverizedpotassium hydroxide (11.2 g) was added to the resultant solution. Afterstirring at room temperature for 20 hours, the reaction mixture waspoured into ice-water (500 ml) and extracted with ethyl acetate (500ml×2). The extract was washed with 1N hydrochloric acid, water, andsaturated aqueous sodium chloride, dried over anhydrous magnesiumsulfate, and the residue obtained by evaporation of the solvent under areduced pressure was purified by medium pressure column chromatographyusing silica gel, to obtain ethyl 2-(4-benzyloxyphenoxy)propionate (57.3g).

The benzyl ether (57.3 g) was dissolved in ethanol (100 ml), the benzylgroup was removed by catalytic reduction with an addition ofpalladium-carbon (6.0 g), and the solvent was evaporated to obtain ethyl2-(4-hydroxyphenoxy)propionate.

The phenol (21.0 g) and 2,3-dichloro-5-trifluoromethyl pyridine (21.6 g)were dissolved in dry dimethyl sulfoxide (150 ml), and anhydrouspotassium carbonate (13.8 g) was added to the resultant solution,followed by stirring at 100° C. for 3 hours. The reaction mixture waspoured into ice-water (300 ml), extracted with ethyl acetate (300 ml×2),and the extract was washed with 1N hydrochloric acid, water, andsaturated aqueous sodium chloride, and dried over anhydrous magnesiumsulfate. The residue obtained by evaporation of the solvent under areduced pressure was purified by medium pressure column chromatographyusing silica gel, to obtain ethyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate (31.0g).

The ester (25.0 g) was dissolved in methanol (100 ml) added with 1Nsodium hydroxide (77 ml), and the reaction was carried out at roomtemperature for 3 hours. Methanol was evaporated under a reducedpressure, the residue was washed with ether (200 ml), and then madeacidic with addition of 1N hydrochloric acid and extracted with ether(200 ml×2). After drying over anhydrous magnesium sulfate, the solventwas evaporated under a reduced pressure to obtain2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid(20.5 g) (m.p. 108° C.-110° C.).

The carboxylic acid (1.5 g) was dissolved in dry benzene (10 ml) andrefluxed, with an addition of thionyl chloride (5 ml), for 2 hours.Evaporation of the solvent and thionyl chloride gave2-(4-3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride hydrochloride (1.5 g).

By using 2-chloro-5-trifluoromethylpyridine instead of2,3-dichloro-5-trifluoromethylpyridine in the above (b),2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride was obtained.

REFERENCE EXAMPLE 2: SYNTHESIS OF THE STARTING MATERIAL HAVING THEFORMULA (3-1) (A) 4-(4-Nitrophenoxy)phenol:

4-Bromonitrobenzene (4.0 g), hydroquinone monomethyl ether (3.1 g),potassium hydroxide (1.5 g) and copper powder (0.1 g) were mixed and thereaction was carried out at 160° C. to 200° C. for 3 hours. Aftercooling to room temperature, the reaction mixture was extracted withbenzene (100 ml), and the extract was washed with 1N sodium hydroxide,water, and saturated aqueous sodium chloride. After drying overmagnesium sulfate, the solvent was evaporated under a reduced pressureand the residue obtained was purified by medium pressure columnchromatography using silica gel, to obtain 4-(4-nitrophenoxy)phenolmethyl ether (1.5 g).

The methyl ether obtained (0.4 g) was dissolved in dry methylenechloride (5 ml), and the resultant solution was added to a solution ofboron trifluoride (0.5 g) in dry methylene chloride (5 ml), followed bystirring at room temperature for 2 hours. After an addition of water,the mixture was extracted with ether (30 ml) and dried over anhydrousmagnesium sulfate to obtain 4-(4-nitrophenoxy)phenol (0.4 g) (m.p.172.9° C.-173.5° C.).

In the above (A), instead of 4-bromonitrobenzene, (a)2-bromonitrobenzene, (b) 2,4-dichloronitrobenzene, (c)3,4-dichloronitrobenzene, (d) 4-bromochlorobenzene, (e)4-bromocyanobenzene, (a') 4-(2-nitrophenoxy)phenol (m.p. 103° C.-105°C.), (b') 4-(3-chloro-4-nitrophenoxy)phenol (m.p. 113° C.-115° C.), (c')4-(2-chloro-4-nitrophenoxy)phenol (m.p. 149° C.-151° C.), (d')4-(4-chlorophenoxy)phenol (m.p. 81.5° C.-83.5° C.), (e')4-(4-cyanophenoxy)phenol (m.p. 148.5° C.-149.5° C.) were obtainedrespectively.

Also, according to the same method, by using2-bromo-3-chloro-5-trifluoromethylpyridine,4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenol was obtained.

(B) 4-(4-Nitrophenoxy)aniline:

p-Acetoaminophenol (1.5 g) and 4-bromonitrobenzene (2.0 g) weredissolved in dry dimethyl sulfoxide (15 ml) and anhydrous potassiumcarbonate (1.4 g) was added, followed by stirring at 100° C. for 3hours. The reaction mixture was poured into ice-water (30 ml), extractedwith ethyl acetate (30 ml×2), and the extract was washed with 1Nhydrochloric acid, water, and saturated aqueous sodium chloride,followed by drying over anhydrous magnesium sulfate. The residueobtained by evaporation of the solvent under a reduced pressure waspurified by medium pressure column chromatography using silica gel, toobtain 4-(4-nitrophenoxy)acetanilide (2.0 g).

The acetanilide (1.9 g) was dissolved in methanol (5 ml), and refluxed,with an addition of 4N hydrochloric acid (7 ml), for 1 hour. Aftercooling to room temperature, methanol was evaporated under a reducedpressure, and the residue was made basic with an addition of 1N sodiumhydroxide and extracted with ethyl acetate (30 ml×2). After drying overanhydrous sodium sulfate, the solvent was evaporated under a reducedpressure to obtain 4-(4-nitrophenoxy)aniline (1.6 g) (m.p. 132.5°C.-134° C).

In the above (B), 4-bromonitrobenzene was replaced with2,3-dichloro-5-trifluoromethylpyridine to obtain4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)aniline.

EXAMPLE 1-1 4-(4-Nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate

2-(4-(4-Chlorophenoxy)phenoxy)propionic acid chloride (0.6 g) and4-(4-nitrophenoxy)phenol (0.5 g) were dissolved in dry tetrahydrofuran(10 ml), and the solution was stirred with an addition of triethylamine(0.3 ml) at room temperature for 2 hours. After completion of thereaction, the solvent was evaporated under a reduced pressure, theresidue was dissolved in methylene chloride (20 ml), and washed with 1Nhydrochloric acid, water, saturated aqueous sodium hydrogen carbonate,water, and aqueous saturated sodium chloride. After drying overanhydrous magnesium sulfate, the solvent was evaporated and the residueobtained was purified by medium pressure column chromatography to obtain4-(4-nitrophenoxy)phenyl 2-(4-(4-chlorophenoxy)phenoxy)propionate (0.8g)

EXAMPLE 1-2 4-(2-Nitrophenoxy)phenyl 2-(4-(4-chlorophenoxy)phenoxy)propionate

In Example 1-1, by using 4-(2-nitrophenoxy)phenol instead of the4-(4-nitrophenoxy)phenol used in Example 1-1, 4-(2-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-3 4-(3-Chloro-4-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate

In Example 1-1, by using of 4-(3-chloro-4-nitrophenoxy)phenol instead ofthe 4-(4-nitrophenoxy)phenol used in Example 1-1,4-(3-chloro-4-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-4 4-(2-Chloro-4-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate

In Example 1-1, by using of 4-(2-chloro-4-nitrophenoxy)phenol instead ofthe 4-(4-nitrophenoxy)phenol used in Example 1-1,4-(2-chloro-4-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-5 4-(4-Chlorophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate

In Example 1-1, by using of 4-(4-chlorophenoxy)phenol instead of the4-(4-nitrophenoxy)phenol used in Example 1-1, 4-(4-chlorophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-6 4-(4-Cyanophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate

In Example 1-1, by using of 4-(4-cyanophenoxy)phenol instead of the4-(4-nitrophenoxy)phenol used in Example 1-1, 4-(4-cyanophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-7 4-Phenoxyphenyl 2-(4-(4-chlorophenoxy)phenoxy propionate

In Example 1-1, by using of 4-phenoxyphenol instead of the4-(4-nitrophenoxy)phenol used in Example 1-1, 4-phenoxyphenyl2-(4-(4-chlorophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-8 4-(4-Nitrophenoxy)phenyl 4-(4-chlorophenoxy)phenoxyacetate

In Example 1-1, by using 4-(4-chlorophenoxy)phenoxyacetic acid chlorideinstead of 2-(4-(4-chlorophenoxy)pheoxy)propionic acid chloride,4-(4-nitrophenoxy)phenyl 4-(4-chlorophenoxy)phenoxyacetate was obtained.

EXAMPLE 1-9 4-(4-Nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)butyrate

In Example 1-1, by using 2-(4-(4-chlorophenoxy)phenoxy)butyric acidchloride instead of 2-(4-(4-chlorophenoxy)phenoxy)propionic acidchloride, 4-(4nitrophenoxy)phenyl 2-(4-(4-chlorophenoxy)phenoxy)butyratewas obtained.

EXAMPLE 1-10 4-(4-Nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)valerate

In Example 1-1, by using 2-(4-(4-chlorophenoxy)phenoxy)valeric acidchloride instead of 2-(4-(4chlorophenoxy)phenoxy)propionic acidchloride, 4-(4-nitrophenoxy)phenyl2-(4-(4-chlorophenoxy)phenoxy)valerate was obtained.

EXAMPLE 1-11 4-(4-Nitrophenoxy)phenyl2-(4-(4-nitrophenoxy)phenoxy)propionate

In Example 1-1, by using 2-(4-(4-nitrophenoxy)phenoxy)propionic acidchloride instead of 2-(4-(4-chlorophenoxy)phenoxy)propionic acidchloride, 4-(4-nitrophenoxy)phenyl2-(4-(4-nitrophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-12 4-(4-Nitrophenoxy)phenyl2-(4-4-phenoxyphenoxy)phenoxy)propionate

In Example 1-1, by using 2-(4-(4-phenoxyphenoxy)phenoxy)propionic acidchloride instead of 2-(4-(4-chlorophenoxy)phenoxy)propionic acidchloride, 4-(4-phenoxyphenoxy)phenyl2-(4-(4-nitrophenoxy)phenoxy)propionate was obtained.

EXAMPLE 1-13 4-(4-Nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxypropionic acidchloride hydrochloride (0.7 g) and 4-(4-nitrophenoxy)phenol (0.5 g) weredissolved in dry tetrahydrofuran (10 ml), and stirred with an additionof triethylamine (0.5 ml) at room temperature for 2 hours. Aftercompletion of the reaction, the solvent was evaporated under a reducedpressure and the residue was dissolved in methylene chloride (20 ml),followed by washing with 1N hydrochloric acid, water, saturated aqueoussodium hydrogen carbonate, water and saturated aqueous sodium chloride.After drying over anhydrous magnesium sulfate, the solvent wasevaporated under a reduced pressure and the residue obtained waspurified by medium pressure column chromatography by using silica gel,to obtain 4-(4-nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate (0.9 g)(oily product).

EXAMPLE 1-14 4-(2-Nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using 4-(2-nitrophenoxy)phenol instead of4-(4-nitrophenoxy)phenol, 4-(2-nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate wasobtained.

EXAMPLE 1-15 4-(3-Chloro-4-nitrophenoxy)phenyl2-(4-(3-chloro5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using 4-(3-chloro-4-nitrophenoxy)phenol instead of4-(4-nitrophenoxy)phenol, 4-(3-chloro-4-nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate wasobtained.

EXAMPLE 1-16 4-(2-Chloro-4-nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using 4-(2-chloro-4-nitrophenoxy)phenol instead of4-(4-nitrophenoxy)phenol, 4-(2-chloro-4-nitrophenoxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate wasobtained.

EXAMPLE 1-17 4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy))phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1 - 13, by using4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenol instead of4-(4-nitrophenoxy)phenol,4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate wasobtained.

EXAMPLE 1-184-(2-(4-(3-Chloro-5-trifluoromethyl)-2-pyridyloxy)phenoxy)propionyl)amino-(4-nitrophenoxy)benzene

In Example 1-13, by using 4-(4-nitrophenoxy)aniline instead of4-(4-nitrophenoxy)phenol,4-(2-(4-(3-chloro-5-trifluoromethyl)-2-pyridyloxy)phenoxy)propionyl)amino-(4-nitrophenoxy)benzenewas obtained.

EXAMPLE 1-194-(2-(4-(3-Chloro-5-trifluoromethyl)-2-pyridyloxy)phenoxy)propionyl)amino-(3-chloro-5-trifluoromethyl-2-pyridyloxy)benzene

In Example 1-13, by using4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)aniline instead of4-(4nitrophenoxy)phenol,4-(2-(4-(3-chloro-5-trifluoromethyl)-2-pyridyloxy)phenoxy)propionyl)amino-(3-chloro-5-trifluoromethyl-2-pyridyloxy)benzenewas obtained.

EXAMPLE 1-20 4-(4-Nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxypropionic acidchloride hydrochloride, 4-(4-nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate was obtained.

EXAMPLE 1-21 4-(2-Nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using2-(4-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxypropionic acidchloride hydrochloride, and 4-(2-nitrophenoxy)phenol instead of4-(4-nitrophenoxy)phenol, 4-(4-nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate was obtained.

EXAMPLE 1-22 4-(3-Chloro-4-nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride hydrochloride, and4-(3-chloro-4-nitrophenoxy)phenyl-2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionatewas obtained.

EXAMPLE 1-23 4-(2-Chloro-4-nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

In Example 1-13, by using2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride hydrochloride, and 4-(2-chloro-4-nitrophenoxy)phenol instead of4-(4-nitrophenoxy)phenol, 4-(2-chloro-4-nitrophenoxy)phenyl2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate was obtained.

The physicochemical data of the compounds obtained is shown in Table 1.

                                      TABLE 1                                     __________________________________________________________________________     ##STR34##                                                                    Example                                                   Yield               No.   Q.sup.1                                                                          Q.sup.2                                                                          X  Y R   Z V.sup.1, V.sup.2                                                                  Properties                                                                             NMR Spectrum/δ ppm                                                                            (%)Hz)              __________________________________________________________________________    1-1   CH CH Cl H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       Oily substance                                                                         (CDCl.sub.3) 1.77(3H, d, J=6.6),                                              4.92(1H, q,           79                                         H            J=6.6), 6.73-8.17(16H, m)                 1-2   CH CH Cl H CH.sub.3                                                                          O 2-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.77(3H, d, J=6.6),                                              4.91(1H, q,           79                                         H            J= 6.6), 6.72-7.94(16H, m)                1-3   CH CH Cl H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.77(3H, d, J=7.2),                                              4.90(1H, q,           74                                         3-Cl         J=7.2), 6.72-7.94(15H, m)                 1-4   CH CH Cl H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.83(3H, d, J=7.2),                                              4.96(1H, q,           77                                         2-Cl         J=7.2), 6.77-8.33(15H, m)                 1-5   CH CH Cl H CH.sub.3                                                                          O 4-Cl,                                                                             "        (CDCl.sub.3) 1.76(3H, d, J=7.2),                                              4.89(1H, q,           79                                         H            J=7.2), 6.72-7.30(16H, m)                 1-6   CH CH Cl H CH.sub.3                                                                          O 4-CN,                                                                             Oily substance                                                                         (CDCl.sub.3) 1.77(3H, d, J=6.6),                                              4.92(1H, q,           85                                         H            J=6.6), 6.73-7.60(16H, m)                 1-7   CH CH Cl H CH.sub.3                                                                          O H, H                                                                              "        (CDCl.sub.3) 1.76(3H, d, J=7.2),                                              4.87(1H, q,           88                                                      J=7.2), 6.72-7.26(17H, m)                 1-8   CH CH Cl H H   O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 4.84(2H, S),                                                     6.73-8.22(16H, m)     62                                         H                                                      1-9   CH CH Cl H C.sub.2 H.sub.5                                                                   O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.16(3H, t, J=6.6),                                              2.14(2H, m),          40                                         H            4.47(1H, t, J=6.0), 6.67-8.09(16H, m)     1-10  CH CH Cl H n-C.sub.3 H.sub.7                                                                 O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.05(3H, t, J=6.6),                                              1.30-2.34             20                                         H            (4H, m), 4.81(1H, t, J=6.6),                                                  6.57-8.16                                                                     (16H, m)                                  1-11  CH CH NO.sub.2                                                                         H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.84(3H, d, J=6.6),                                              5.04(1H, q,           80                                         H            J=6.6), 6.70-8.20(16H, m)                 1-12  CH CH H  H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       Oily substance                                                                         (CDCl.sub.3) 1.77(3H, d, J=7.2),                                              4.93(1H, q,           56                                         H            J=7.2), 6.79-8.17(17H, m)                 1-13  N  CH CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.81(3H, d, J=6.6),                                              4.97(1H, q,           97                                         H            J=6.6), 6.88-8.21(14H, m)                 1-14  N  CH CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          O 2-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.78(3H, d, J=7.2),                                              4.96(1H, q,           86                                         H            J=7.2), 6.86-8.20(14H, m)                 1-15  N  CH CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.79(3H, d, J=6.6),                                              4.96(1H, q,           66                                         3-Cl         J=6.6), 6.74-8.20(13H, m)                 1-16  N  CH CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.82(3H, d, J=7.0),                                              5.02(1H, q,           68                                         2-Cl         J=7.0), 6.86-8.36(13H, m)                 1-17  N  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          O 3-Cl,                                                                             "        (CDCl.sub.3) 1.90(3H, d, J=7.0),                                              5.09(1H, q,           72                                         5-CF.sub.3   J=7.0), 7.17-8.36(12H, m)                 1-18  N  CH CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          N 4-NO.sub.2,                                                                       Oily substance                                                                         (CDCl.sub.3) 1.70(3H, d, J=6.6),                                              4.79(1H, q,           98                                         H            J=6.6), 6.87-8.24(14H, m), 8.36(1H,                                           s)                                        1-19  N  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          N 3-Cl,                                                                             "        (CDCl.sub.3) 1.72(3H, d, J=7.0),                                              4.82(1H, q,           75                                         5-CF.sub.3   J=7.0), 7.08-8.30(13H, m)                 1-20  N  CH CF.sub.3                                                                         H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.79(3H, d, J=6.6),                                              4.95(1H, q,           40                                         H            J=6.6), 6.82-7.34(15H, m)                 1-21  N  CH CF.sub.3                                                                         H CH.sub.3                                                                          O 2-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.79(3H, d, J=6.6),                                              4.97(1H, q,           89                                         H            J=6.6), 6.86-8.37(15H, m)                 1-22  N  CH CF.sub.3                                                                         H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.80(3H, d, J=6.6),                                              4.96(1H, q,           93                                         3-Cl         J=6.6), 6.86-8.36(14H, m)                 1-23  N  CH CF.sub.3                                                                         H CH.sub.3                                                                          O 4-NO.sub.2,                                                                       "        (CDCl.sub.3) 1.82(3H, d, J=7.0),                                              5.02(1H, q,           74                                         2-Cl         J=7.0), 6.84-8.41(14H,                    __________________________________________________________________________                                        m)                                    

REFERENCE EXAMPLE 3: SYNTHESIS OF STARTING MATERIAL HAVING THE FORMULA(3-2) (A) 4-Aminobenzenesulfonamide

To 4-nitrobenzenesulfonyl chloride (6.7 g) was added ammonia water (10ml) while ice-cooling, and the mixture was stirred at room temperaturefor 3 hours. The reaction mixture was extracted with ethyl acetate (100ml), and the extract was washed with water and saturated aqueous sodiumchloride and dried over anhydrous sodium sulfate, followed byevaporation of the solvent under a reduced pressure, to obtain4-nitrobenzenesulfonamide (5.9 g).

The 4-nitrobenzenesulfonamide obtained (5.9 g) was dissolved in methanol(100 ml), and after an addition of conc. hydrochloric acid, reduced iron(4.2 g) was added and the mixture stirred at room temperature for 2hours. After filtration, methanol was evaporated under a reducedpressure, the residue was made basic with an addition of 4N sodiumhydroxide, and the mixture of the desired product and iron oxideprecipitated was collected by filtration. The mixture was dissolved inacetone (200 ml), filtered to remove iron oxide, and the solvent wasevaporated under a reduced pressure to obtain 4-aminobenzenesulfonamide(3.7 g) (m.p. 164° C.-165.5° C.).

By using (a) 2-nitrobenzenesulfonyl chloride, (b) 3-nitrobenzenesulfonylchloride instead of 4-nitrobenzenesulfonyl chloride in the above (A),(a') 2-aminobenzenesulfonamide (m.p. 184° C.-186° C.), (b')3-aminobenzenesulfonamide (m.p. 139° C. -140° C.) were obtainedrespectively.

(B) N-methyl-4-(amino)benzenesulfonamide

To a solution of methylamine hydrochloride (1.4 g) in pyridine (5 ml)was added 4-acetamidobenzenesulfonyl chloride (2.3 g), and the mixturewas stirred at 50° C. for 2 hours. The residue obtained by anevaporation of pyridine under a reduced pressure was dissolved inmethylene chloride (50 ml), washed with water, 1N hydrochloric acid, andsaturated aqueous sodium chloride, and dried over anhydrous sodiumsulfate. Evaporation of the solvent under a reduced pressure gaveN-methyl-4-(acetamido)benzenesulfonamide (1.6 g).

The acetamide (1.6 g) was dissolved in methanol (5 ml) and refluxed,with an addition of 4N hydrochloric acid (7 ml), for 1 hour. After anevaporation of methanol under a reduced pressure, the residue was madebasic with an addition of 1N sodium hydroxide, and extracted with ethylacetate (30 ml), followed by drying over anhydrous sodium sulfate.Evaporation of the solvent under a reduced pressure gaveN-methyl-4-(amino)benzenesulfonamide (1.2 g) (m.p. 110.9° C.-112° C.).

In the above (B), instead of methylamine hydrochloride, (a)O,N-dimethylhydroxylamine hydrochloride, (b) diethylamine were employedto obtain (a') N-methyl-N-methoxy-4-(amino)benzenesulfonamide (m.p. 119°C.-120° C.), (b') N,N-diethyl-4-(amino)benzenesulfonamide (m.p. 102°C.-103.5° C.), respectively.

(C) N,N,Diethyl-3-(amino)benzenesulfonamide

Diethylamine (2.4 g) was dissolved in pyridine (15 ml) and3-nitrobenzenesulfonyl chloride (6.7 g) was added, followed by stirringat 50° C. for 2 hours. The residue obtained by an evaporation ofpyridine under a reduced pressure was dissolved in methylene chloride(150 ml), washed with water, 1N hydrochloric acid, water, and saturatedaqueous sodium chloride, and dried over anhydrous sodium sulfate.Evaporation of the solvent under a reduced pressure gaveN,N-diethyl-3-(nitro)benzenesulfonamide (4.0 g).

The N,N-diethyl-3-(nitro)benzenesulfonamide (3.9 g) was dissolved inmethanol (60 ml) and, after an addition of conc. hydrochloric acid (10ml), reduced iron (4.2 g) was added and the mixture was stirred at roomtemperature for 2 hours. After filtration, methanol was evaporated undera reduced pressure and the residue was made basic with an addition of 4Nsodium hydroxide. The iron oxide precipitated was separated byfiltration, washed with methylene chloride (50 ml). Also the filtratewas extracted with methylene (50 ml×2) and combined with the methylenechloride washing, followed by drying over anhydrous sodium sulfate.Evaporation of the solvent gave N,N-diethyl-3-(amino)benzenesulfonamide(3.0 g) (m.p. 82°-84° C.).

EXAMPLE 2-14-(2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamido)benzenesulfonamide

(2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride hydrochloride (0.8 g) and 4-aminobenzene sulfonamide (0.5 g)were dissolved in dry tetrahydrofuran (20 ml), and the solution wasstirred, with an addition of triethylamine (0.6 ml) at room temperaturefor 2 hours. After completion of the reaction, the solvent wasevaporated under a reduced pressure, the residue was dissolved inmethylene chloride and washed with 1N hydrochloric acid, water,saturated aqueous sodium hydrogen carbonate, water and saturated aqueoussodium chloride. After drying over anhydrous sodium sulfate, the residueobtained by evaporation of the solvent under a reduced pressure waspurified by medium pressure column chromatography by using silica gel,to obtain the title compound (0.8 g).

EXAMPLE 2-23-(2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamido)benzenesulfonamide

In Example 2-1, by using 3-aminobenzene sulfonamide instead of4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-32-(2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamide)benzenesulfonamide

In Example 2-1, by using 2-aminobenzenesulfonamide instead of4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-4N-Methyl-4-(2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamido)benzenesulfonamide

In Example 2-1, by using N-methyl-4-(amino)benzenesulfonamide instead of4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-6N-Methyl-N-methoxy-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamido)benzenesulfonamide

In Example 2-1, by using N-methyl-N-methoxy-4-(amino)benzenesulfonamideinstead of 4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-7N-(Methoxycarbonyl)4-(2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamide)benzenesulfonamide

In Example 2-1, by using N-(methoxycarbonyl)-4-(amino)benzenesulfonamideinstead of 4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-8N,N-diethyl-3-(2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propanamide)benzenesulfonamide

In Example 2-1, by using N,N-diethyl-3-4(amino)benzenesulfonamideinstead of 4-aminobenzenesulfonamide, the title compound was obtained.

EXAMPLE 2-94-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxyacetamide)benzenesulfonamide

In Example 2-1, by using4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxyacetic acid chloridehydrochloride instead of 2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid chloridehydrochloride, the title compound was obtained.

EXAMPLE 2-104-(2-(4-(5-Trifluoromethyl-2-pyridyloxy)phenoxy)propanamide)benzenesulfonamide

In Example 2-1, by using2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxypropionic acid chloridehydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride hydrochloride, the title compound was obtained.

EXAMPLE 2-114-(2-(4-(4-Chlorophenoxy)phenoxy)propanamido)benzenesulfonamide

In Example 2-1, by using 2-(4-(4-chlorophenoxy)phenoxy)propionic acidchloride hydrochloride instead of2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride, the title compound was obtained.

The physicochemical data of the compounds obtained is shown in Table 2.

                                      TABLE 2                                     __________________________________________________________________________     ##STR35##                                                                    Example                                           Yield                       No.  Q.sup.1                                                                          X  Y R  NR.sup.1 R.sup.2                                                                      Property                                                                            NMR Spectrum/δ ppm (J/Hz)                                                                   (%)                         __________________________________________________________________________    2-1  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         4,NH.sub.2                                                                            mp    (CD.sub.3 OD)1.66(3H, d, J=6.6), 4.86 (1H,                                    q,                  78                                                  195-97° C.                                                                   J=6.6), 7.08-8.23(10H, m)                       2-2  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         3,NH.sub.2                                                                            Oily  (CDCl.sub.3)1.63(3H,d,J=7.0), 4.76(1H,                                                            53                                                  substance                                                                           J=7.0), 5.38(2H, s), 6.93-8.22(10H, m),                                       8.58(1H, s)                                     2-3  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         2,NH.sub.2                                                                            Oily  (CDCl.sub.3)1.70(3H, d, J= 7.0), 4.78(1H,                                     q,                  61                                                  substance                                                                           J=7.0), 4.91(2H, s), 6.98-8.42(10H, m),                                       10.12(1H, s)                                    2-4  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         4,NHCH.sub.3                                                                          Oily  (CDCl.sub.3)1.62(3H, d, J=6.0), 2.56(3H,                                                          98                                                  substance                                                                           J=5.4), 4.65(1H, q, J=5.4), 4.74(1H, q,                                       J=6.0), 6.98-8.17(10H, m), 8.42(1H, s)          2-5  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                          ##STR36##                                                                            Oily substance                                                                      (CDCl.sub.3)1.58(3H, d, J=6.0), 2.60(3H,                                      s), 3.61(3H, s), 4.61(1H, q, J=6.0),                                          6.70-8.04(10H, m), 8.37(1H,                                                                       99                          2-6  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         4,N(C.sub.2 H.sub.5).sub.2                                                            Oily  (CDCl.sub.3)1.10(6H, t, J=7.0), 1.64(3H,                                                          94                                                  substance                                                                           J=7.0), 3.18(4H, q, J=7.0), 4.76(1H, q,                                       J=7.0), 6.94-8.22(10H, m), 8.42(1H, s)          2-7  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         4,NHCO.sub.2 CH.sub.3                                                                 mp    (CD.sub.3 OD)1.63(3H, d, J=7.2), 3.60(3H,                                     s),                 96                                                  214- 216° C.                                                                 4.74(1H, q, J=7.2), 7.03-8.20(10H, m)           2-8  N  CF.sub.3                                                                         Cl                                                                              CH.sub.3                                                                         3,N(C.sub.2 H.sub.5).sub.2                                                            Oily  (CDCl.sub.3)1.16(6H, 5, J=7.0), 1.69(3H,                                                          92                                                  substance                                                                           J=7.0), 3.27(4H, q, J=7.0), 4.81(1H, q,                                       J=7.0), 6.97-8.26(10H, m), 8.54(1H, s)          2-9  N  CF.sub.3                                                                         Cl                                                                              H  4,NH.sub.2                                                                            mp 205-                                                                             (Acetone-d.sub.6)4.76(2H, s), 6.49(2H,                                                            55,                                                 206.5° C.                                                                    7.05-8.37(10H, m)                                2-10                                                                              N  CF.sub.3                                                                         H CH.sub.3                                                                         4,NH.sub.2                                                                            mp 173.5-                                                                           (Acetone-d.sub.6)1.62(3H, d,                                                                      657.0),                                             175° C.                                                                      4.91(1H, q, J=7.0), 6.51(2H, s),                                              7.12-8.44(11H, m), 9,67(1H, s)                   2-11                                                                              CH Cl H CH.sub.3                                                                         4,NH.sub.2                                                                            mp 198-                                                                             (Acetone-d.sub.6)1.61(3H, d,                                                                      507.0),                                             199.5° C.                                                                    4.87(1H, q, J=7.0), 6.47(2H, s),                                              6.88-7.95(12H, m), 9.62(1H,                     __________________________________________________________________________                                  s)                                          

EXAMPLE 3-1 (3-Bromo-2-oxo)propyl2-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]propionate

2-[4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)-phenoxy]propionic acid(1.6 g) was dissolved in 10 ml of dimethylformamide, and the solutionwas stirred with an addition of 1 ml of dicyclohexylamine at 40° C.Then, 710 mg of 3-chlorodiazoacetone was added dropwise, and the mixturewas further stirred for 2 hours. The reaction mixture was washed withwater, extracted with ether, and the extract was dried over anhydrousmagnesium sulfate. The oily product obtained by evaporation of etherunder a reduced pressure was subjected to silica gel medium pressurecolumn chromatography (n-hexane/ethyl acetate), to obtain 1.32 g of adiazomethylketone derivative as a colorless oily product.

The compound (300 mg) as prepared above was dissolved in 10 ml of ether,and 230 mg of 47% hydrobromic acid was added, followed by stirring for30 minutes. The reaction mixture was washed with water, dried overanhydrous magnesium sulfate, and ether was evaporated under a reducedpressure to give 270 mg of the title compound as a colorless oilyproduct.

EXAMPLE 3-2 (3,3-Dibromo-2-oxo)propyl2[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]propionate

The synthetic intermediate (3-diazo-12-oxopropyl)2[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]propionate (300 mg)was dissolved in 40 ml of carbon tetrachloride, and a solution of 22 mgof bromine in 5 ml of carbon tetrachloride was added at 0° C. Afterstirring for 30 minutes, the solvent was evaporated under a reducedpressure, and the residue was subjected to silica gel medium pressurecolumn chromatography (n-hexane/ethyl acetate), to obtain 200 mg of thetitle compound as a colorless oily product.

EXAMPLE 3-3 (3-Chloro-2-oxo)propyl4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxyacetate

4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxyacetic acid (1.7 g)was dissolved in 30 ml of dimethylformamide, the solution was stirredwith an addition of 1 ml of dicyclohexylamine at 60° C., added into 30ml of a solution of 1.9 g of 1,3-dichloroacetone in dimethylformamide,and the mixture was further stirred for 2 hours. After the reaction, theproduct was washed with water, extracted with ethyl acetate, and theextract washed with 1N hydrochloric acid, followed by drying overanhydrous magnesium sulfate. The oily product obtained by evaporation ofthe solvent under a reduced pressure was subjected to silica gel mediumpressure column chromatography (n-hexane/ethyl acetate), to obtain 1.45g of the title compound as a colorless oily product.

EXAMPLE 3-4N-[2-{4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionyl]alaninechloromethyl ketone

N-[2-{4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionylalanine(400 mg) was dissolved in 10 ml of tetrahydrofuran, added with 0.15 mlof triethylamine and cooled to 0° C. Ethyl chlorocarbonate (0.1 ml) wasadded and after 5 minutes, excessive diazomethane ether solution wasadded, and the mixture was stirred for one hour. Then, several drops ofconc. hydrochloric acid were added and, after stirring for 10 minutes,the reaction mixture was washed with water, extracted with ether, andthe extract dried over anhydrous magnesium sulfate. The oily productobtained by evaporation of the solvent under a reduced pressure wassubjected to silica gel medium pressure column chromatography to obtain300 mg of the title compound as a colorless oily product.

EXAMPLE 3-5 (3-Chloro-2oxo-1,1-dimethyl)propyl2-[4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy]propionate

2-[2-{4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionyloxy]isobutyricacid (3.1 g) was dissolved in 50 ml of benzene, 2 ml of thionyl chloridewas added to the solution, and the mixture was stirred under heating at90° C. for one hour. Benzene was evaporated under a reduced pressure, asmall amount of ether was added and excessive diazomethane ethersolution was added while cooling. After stirring for one hour, whilehydrogen chloride gas was passed therethrough, the mixture was stirredat room temperature for 30 minutes. The reaction mixture was washed withwater, dried over anhydrous magnesium sulfate and the solvent wasevaporated under a reduced pressure. The oily product obtained wassubjected to silica gel medium pressure column chromatography(n-hexane/ethyl acetate) to obtain 3.4 g of the title product as acolorless oily product.

According to the same method as described above in Examples 3-1 to 3-5,the compounds of Example Nos. 3-6 to 3-9 were synthesized by usingpreparation method A, the compounds of Example Nos. 3-10 to 3-15 byusing preparation method B and the compounds of Example Nos. 3-16 to3-18, respectively.

The physical property values of the compounds synthesized above areshown in Table 3.

                                      TABLE 3                                     __________________________________________________________________________     ##STR37##                                                                    Example                                                                       No.   Y X.sup.1                                                                         R  R.sup.3                                                                          R.sup.4                                                                           R.sup.5                                                                          R.sup.6                                                                          Z  Q.sup.1                                                                          Property                                      __________________________________________________________________________    3-1   Cl                                                                              Br                                                                              Me H  H   H  H  O  N  n.sub.D.sup.25 1.4960                         3-2   Cl                                                                              Br                                                                              Me H  H   H  Br O  N  n.sub.D.sup.25 1.5123                         3-3   Cl                                                                              Cl                                                                              H  H  H   H  H  O  N  m.p. 118° C.                           3-4   Cl                                                                              Cl                                                                              Me Me H   H  H  NH N  m.p. 119° C.                           3-5   Cl                                                                              Cl                                                                              Me Me Me  H  H  O  N  m.p. 76° C.                            3-6   Cl                                                                              Br                                                                              Me H  H   H  H  O  CH n.sub. D.sup.25 1.5367                        3-7   Cl                                                                              Cl                                                                              Me Me H   H  H  O  N  n.sub.D.sup.25 1.5220                         3-8   Cl                                                                              I Me H  H   H  H  O  N  n.sub.D.sup.25 1.5233                         3-9   Cl                                                                              Br                                                                              Me Me H   H  H  O  N  n.sub.D.sup.25 1.5236                         3-10  Cl                                                                              Cl                                                                              Me H  H   H  H  O  CH n.sub.D.sup.25 1.5068                         3-11  Cl                                                                              Cl                                                                              Me H  H   H  H  O  N  n.sub.D.sup.25 1.5287                         3-12  H Cl                                                                              Me H  H   H  H  O  N  n.sub.D.sup.25 1.5225                         3-13  Cl                                                                              Br                                                                              Me H  H   Me Me O  N  n.sub.D.sup.25 1.5222                         3-14  Cl                                                                              Cl                                                                              Me H  H   Me H  O  N  n.sub.D.sup.25 1.5184                         3-15  Cl                                                                              F Me H  H   H  H  O  N  n.sub.D.sup.25 1.5089                         3-16  Cl                                                                              Cl                                                                              H  Me Me  H  H  NH N  m.p. 83° C.                            3-17  Cl                                                                              Cl                                                                              Me Me Me  H  H  NH N  m.p. 81° C.                            3-18  H Cl                                                                              H  Me Me  H  H  O  N  m.p. 111° C.                           __________________________________________________________________________     n.sub.D.sup.25 = Index of Refraction, m.p. = melting point, Me =  CH.sub.                                                                              

EXAMPLE 4-1 {3-(4-Chlorophenoxy)-2-oxo)propyl2-{4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionate

2-{4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionic acid(724 mg) was dissolved in 20 ml of dimethylformamide, 0.4 ml ofdicyclohexylamine was added to the solution and the mixture was stirredat 50° C. Then, 420 mg of 1-chloro-3-(4-chlorophenoxy)acetone was added,and further stirring was continued at 50° C. for 3 hours. To thereaction mixture was added 30 ml of water, the mixture was extractedwith ethyl acetate and the extract washed with water, followed by dryingover anhydrous magnesium sulfate. The oily product obtained byevaporation of the solvent under a reduced pressure was subjected tosilica gel medium pressure column chromatography [(n-hexane:ethylacetate=6:1 (v/v)], to obtain 600 mg of the title compound as acolorless oily product.

EXAMPLE 4-2 (3-Acetoxy-2-oxo-)propyl2-{4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionate

2-{4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy}propionic acid(1.81 g) was dissolved in 100 ml of dimethylformamide, 1 ml ofdicyclohexylamine was added and the mixture was stirred at 50° C. Then,1.9 g of 1,3-dichloroacetone was added, and the mixture was furtherstirred at 50° C. for 3 hours. To the reaction mixture was added 100 mlof water, the mixture extracted with ethyl acetate, and the extractwashed with water, followed by drying over anhydrous magnesium sulfate.The oily product obtained by evaporation of the solvent under a reducedpressure was subjected to silica gel medium pressure columnchromatography [(n-hexane:ethyl acetate=9:1 (v/v)], to obtain 1.43 g ofa chloromethyl ketone derivative as a colorless oily product.

To a solution of 0.6 ml of acetic acid in 10 ml of dimethylformamide wasadded 0.2 ml of dicyclohexylamine, and the mixture was stirred at 50° C.Then, 452 mg of the above chloromethyl ketone derivative was added, andfurther, the mixture was stirred at 50° C. for 3 hours. To the reactionmixture was added 10 ml of water, the mixture was extracted with ethylacetate, and the extract washed with water, followed by drying overanhydrous magnesium sulfate. The oily product obtained by evaporation ofthe solvent under a reduced pressure was subjected to silica gel mediumpressure column chromatography [(n-hexane:ethyl acetate=9:1 (v/v)], toobtain 310 mg of the title compound as a colorless oily product.

Also, according to the same method as in the above Example 4-1, thefollowing compounds of Example 4-2, 4-4, 4-8, 4-9, 4-10, 4-11, 4-12,4-13, 4-14 and 4-15 were synthesized by using the preparation process A,and according to the same method as in the above Preparation example4-2, the following compounds of Examples 4-5, 4-6 and 4-7 weresynthesized by using the preparation process B.

The structures and the physical property values of the compoundssynthesized above are shown in Table 4.

                                      TABLE 4                                     __________________________________________________________________________     ##STR38##                                                                    Example                                                                       No.   Y R.sup.7                                                                          R.sup.8                                                                          R.sup.9                                                                          R.sup.10                                                                         W.sup.1                                                                          W.sup.2 R.sup.11                                                                       Property                                      __________________________________________________________________________    4-1   Cl                                                                              H  H  H  H  O  4-chlorophenyl                                                                         n.sub.D.sup.25 1.4984                         4-2   Cl                                                                              H  H  H  H  O  CH.sub.3 n.sub.D.sup.25 1.5041                         4-3   Cl                                                                              H  H  H  H  O  COCH.sub.3                                                                             n.sub.D.sup.25 1.4858                         4-4   Cl                                                                              H  H  H  H  O  4-chlorophenoxyl                                                                       n.sub.D.sup.25 1.5349                         4-5   Cl                                                                              H  H  H  H  O  4-benzoyl                                                                              mp 103° C.                             4-6   Cl                                                                              H  H  H  H  O  3-phenylpropionyl                                                                      n.sub.D.sup.25 1.5208                         4-7   Cl                                                                              H  H  H  H  O  COCHCH.sub.2                                                                           n.sub.D.sup.25 1.4996                         4-8   Cl                                                                              H  H  H  H  O  H        n.sub.D.sup.25 1.4930                         4-9   Cl                                                                              Me H  H  H  O  H        n.sub.D.sup.25 1.4812                         4-10  Cl                                                                              Me Me H  H  O  H        n.sub.D.sup.25 1.5130                         4-11  Cl                                                                              H  H  Me Me O  H        n.sub.D.sup.25 1.5024                         4-12  H H  H  H  H  O  H        n.sub.D.sup.25 1.4916                         4-13  Cl                                                                              H  H  H  H  N  COO(t-Bu)                                                                              n.sub.D.sup.25 1.5074                         4-14  Cl                                                                              H  H  Me H  N  COCH.sub.3                                                                             n.sub.D.sup.25 1.5180                         4-15  Cl                                                                              H  H  Me H  N  COCF.sub.3                                                                             n.sub.D.sup.25 1.4989                         __________________________________________________________________________

EXAMPLE 5-12-(4-(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid5-(2,4-dichlorophenoxy)-2-nitrophenyl ester:

5-(2,4-Dichlorophenoxy)-2-nitrophenol (0.8 g) and triethylamine (0.6 ml)were dissolved in dry tetrahydrofuran (10 ml), and the solution wasstirred at room temperature for 2 hours, with an addition of a solutionof 2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acidchloride (0.8 g), in dry tetrahydrofuran (10 ml). After completing thereaction, the solvent was distilled off under a reduced pressure and theresidue was dissolved in methylene chloride (20 ml), followed by washingwith 1N hydrochloric acid, water, a saturated aqueous sodium bicarbonatesolution, water, and a saturated aqueous sodium chloride solution. Theresultant reaction mixture was dried over anhydrous magnesium sulfate,ether was evaporated under a reduced pressure, and the resultant residuewas subjected to silica gel medium pressure column chromatography forpurification. Thus, the title compound (0.9 g) was obtained in the formof a colorless oily product.

The compounds of Examples 4-2 to 4-7 were synthesized in same manner asin Example 4-1.

The physical property data of the resultant compounds is shown in Table5.

                                      TABLE 5                                     __________________________________________________________________________     ##STR39##                                                                    Example No.                                                                            Q.sup.1                                                                           Q.sup.3                                                                           Z    V.sup.3                                                                           R    Property                                       __________________________________________________________________________    5-1      N   CH  O    Cl  CH.sub.3                                                                           n.sub.D.sup.25 1.5163                          5-2      N   N   O    CF.sub.3                                                                          CH.sub.3                                                                           mp 72-74° C.                            5-3      N   CH  O    CF.sub.3                                                                          CH.sub.3                                                                           n.sub.D.sup.25 1.5210                          5-4      CH  CH  O    CF.sub.3                                                                          CH.sub.3                                                                           n.sub.D.sup.25 1.5047                          5-5      N   CH  O    CF.sub.3                                                                          H    n.sub.D.sup.25 1.5024                          5-6      CH  CH  O    CF.sub.3                                                                          H    n.sub.D.sup.25 1.5030                          5-7      N   CH  NH   CF.sub.3                                                                          CF.sub.3                                                                           mp 136-137° C.                          __________________________________________________________________________

EXAMPLE 6-12-(4(3-Chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid2-oxopropyl ester:

2-(4-(3-Chloro-5-trifluoromethyl-2-pyridyl-oxy)phenoxy) propionic acid(3.62 g) was dissolved in dimethylformamide (50 ml) and the solution wasstirred with an addition of dicyclohexylamine (2.2 ml). The mixture wasfurther stirred at a temperature of 60° C. for 3 hours. To the reactionmixture, 100 ml of water was added, followed by extracting with toluene.After washing with water, the mixture was dried over anhydrous magnesiumsulfate, the solvent was distilled off under a reduced pressure, and theresultant oily product was subjected to silica gel medium pressurecolumn chromatography (n-hexane/ethyl acetate=9/1 v/v%) to obtain 4.00 gof the title compound in the form of a colorless oily product(yield=96%).

The compounds of Examples 6-2 to 6-11 were synthesized in the samemanner as in Example 6-1.

The structures and the physical properties of the compounds are shown inTable 6.

                  TABLE 6                                                         ______________________________________                                         ##STR40##                                                                    Example                                                                       No.      Y     R.sup.12                                                                             R.sup.13                                                                            R.sup.14  Property                                ______________________________________                                        6-1      Cl    H      H     CH.sub.3  n.sub.D.sup.25 1.5069                   6-2      Cl    H      H     C.sub.2 H.sub.5                                                                         n.sub.D.sup.25 1.5012                   6-3      Cl    H      H     C.sub.6 H.sub.5                                                                         n.sub.D.sup.25 1.4960                   6-4      Cl    H      CH.sub.2CH.sub.2CH.sub.2                                                                    n.sub.D.sup.25 1.5132                     6-5      Cl    CH.sub.3                                                                             H     CH.sub.3  n.sub.D.sup.25 1.5086                   6-6      Cl    H      H     t-butyl   n.sub.D.sup.25 1.4962                   6-7      Cl    H      H     2,5-dimethoxy-                                                                          mp 65° C.                                                    phenyl                                            6-8      Cl    H      H     4-fluorophenyl                                                                          mp 96° C.                        6-9      Cl    H      H     3,4-dihydroxy-                                                                          n.sub.D.sup.25 1.4903                                               phenyl                                             6-10    Cl    H      H     4-nitrophenyl                                                                           mp 125° C.                        6-11    H     H      H     CH.sub.3  n.sub.D.sup.25 1.4984                   ______________________________________                                    

FORMULATION EXAMPLE 1 (EMULSION)

In the present compound (Compound in Example 3-11), as the activeingredient, (15 parts by weight), 65 parts by weight of xylene, and 20parts by weight of a polyoxyethylene alkyl allyl ether were mixed into ahomogeneous solution to obtain an emulsion containing 15% of the activeingredient. During usage, the emulsion was diluted with water to apredetermined concentration before spraying.

FORMULATION EXAMPLE 2 (WETTABLE AGENT)

In the present compound (Compound in Example 4-8), as the activeingredient, (40 parts by weight), 55 parts by weight of Zieglight, 2parts by weight of sodium alkylbenzenesulfonate and 3 parts by weight ofa poloxyethylene alkyl aryl ether were mixed and pulverized to obtain awettable agent containing 40% of the active ingredient compound. Duringusage, the agent was diluted with water to a predetermined concentrationbefore spraying.

FORMULATION EXAMPLE 3 (GRANULE)

In the present compound (Compound in Example 6-1), as the activeingredient, (5 parts by weight), 20 parts by weight of bentonite, 73parts by weight of clay, and 2 parts by weight of sodiumdodecylbenzenesulfonate were mixed and kneaded with an addition of about20 parts by weight of water by a kneader. The kneaded product wasgranulated through a granulator, and subsequently dried and classifiedinto regular sizes to prepare granules containing 5% of the activeingredient.

TEST EXAMPLE 1: HERBICIDAL ACTIVITY IN UPLAND CONDITIONS (1)Pre-emergence Test

A square pot 7.1×7.1 cm was filled with field soil, and after seeding ofEchinochloa crus-galli, Digitaria ciliaris, covered with 5 mm of soil. Apredetermined amount of the test compound was diluted with water and 10liters/are of the dilution was used for treatment of the soil. After thetreatment, management was performed in a greenhouse for 20 days, and theherbicidal effect was evaluated by observation according to followingstandards, to obtain the results shown in Table 7.

    ______________________________________                                        Mark              Degree of the damage                                        ______________________________________                                        5:                complete death                                              4:                severe                                                      3:                moderate                                                    2:                mild                                                        1:                slight                                                      0:                none                                                        ______________________________________                                    

                                      TABLE 7                                     __________________________________________________________________________    Exam-                                                                             Application                                                                          Herbicidal effect                                                  ple rate   Echinochloa                                                                          Digitaria                                                                          Polygonum                                                                            Amaranthus                                      No. (g/a)  crus-galli                                                                           ciliaris                                                                           lapathifolium                                                                        viridis                                         __________________________________________________________________________    1-2 40     5      4    --     --                                              1-6 40     5      4    --     --                                              1-13                                                                              40     5      5    --     --                                              1-15                                                                              40     5      5    --     --                                              1-22                                                                              40     5      5    --     --                                              2-1 40     5      5    --     --                                              2-2 40     5      5    --     --                                              2-7 40     5      5    --     --                                              3-7 40     5      5    0      0                                               3-10                                                                              20     5      5    0      0                                               3-14                                                                              20     5      5    0      0                                               3-17                                                                              20     5      5    0      0                                               4-2 40     5      5    0      0                                               4-3 20     5      5    0      0                                               4-4 20     5      5    4      4                                               4-8 20     5      5    0      0                                               4-9 20     5      5    0      0                                               4-13                                                                              20     5      5    0      0                                               5-3 20     5      5    4      3                                               5-4 20     3      4    5      4                                               5-6 20     2      3    5      5                                               6-1 20     5      5    0      0                                               6-4 20     5      5    0      2                                               6-6 20     5      5    0      0                                               6-9 20     5      5    0      0                                               6-11                                                                              20     5      5    0      0                                               __________________________________________________________________________

(2) Post-emergence Test

A square pot 7.1×7.1 cm was filled with field soil, and after seeding ofEchinochloa crus-galli, Digitaria ciliaris, covered with 5 mm of soil.Then, the seeds were allowed to geminate at room temperature for 7 days,and a predetermined amount of the test compound was diluted with waterand 10 liters/are of the dilution was used for spraying over the plants.After the treatment, management was performed in a greenhouse for 20days, and the herbicidal effect was evaluated by observation accordingto the same standards as in Test Example 1 to obtain the results shownin Table 8.

                                      TABLE 8                                     __________________________________________________________________________    Exam-                                                                             Application                                                                          Herbicidal effect                                                  ple rate   Echinochloa                                                                          Digitaria                                                                          Polygonum                                                                            Amaranthus                                      No. (g/a)  crus-galli                                                                           ciliaris                                                                           lapathifolium                                                                        viridis                                         __________________________________________________________________________    1-2 40     5      3    --     --                                              1-6 40     5      3    --     --                                              1-13                                                                              40     5      5    --     --                                              1-15                                                                              40     5      4    --     --                                              1-22                                                                              40     5      4    --     --                                              2-1 40     5      3    --     --                                              2-2 40     5      3    --     --                                              2-7 40     5      3    --     --                                              3-7 40     5      5    5      5                                               3-9 20     5      5    0      0                                               3-10                                                                              20     5      5    2      4                                               3-14                                                                              20     5      5    0      0                                               3-17                                                                              40     5      5    0      1                                               4-2 20     5      5    0      0                                               4-3 20     5      5    0      0                                               4-4 20     5      5    3      3                                               4-8 20     5      5    0      0                                               4-9 20     5      5    0      0                                               4-13                                                                              20     5      5    0      0                                               5-3 20     5      5    5      5                                               5-4 20     4      4    5      5                                               5-6 20     1      2    5      5                                               6-1 20     5      5    0      0                                               6-4 20     5      5    2      2                                               6-6 20     5      5    0      2                                               6-9 20     5      5    0      0                                               6-11                                                                              20     5      5    2      3                                               __________________________________________________________________________

TEST EXAMPLE 2: HERBICIDAL ACTIVITY IN PADDY CONDITIONS (1)Pre-emergence Test

A square pot 7.1×7.1 cm was filled with paddy field soil, submerged tothe state of a paddy field, and Echinochloa oryzicola and Monochoriavaginalis were seeded. Then, a predetermined amount of the test compoundin 5 ml/pot of water was applied with a pipette on the water surface.After the treatment, management was performed in a greenhouse for 20days, and the herbicidal effect was evaluated by observation accordingto the same standards as in Test Example 1 to obtain the results shownin Table 9.

                  TABLE 9                                                         ______________________________________                                        Exam- Application                                                                              Herbicidal effect                                            ple   rate       Echinochloa                                                                              Monochoria                                                                              Cyperus                                 No.   (g/a)      oryzicola  vaginalis difformis                               ______________________________________                                        1-2   40         5          0         --                                      1-6   40         5          0         --                                      1-13  40         5          0         --                                      1-15  40         5          0         --                                      1-22  40         5          0         --                                      2-1   40         5          2         --                                      2-2   40         5          3         --                                      2-7   40         5          5         --                                      3-7   40         5          5         --                                      3-9   20         5          5         --                                      3-10  20         5          5         --                                      3-14  20         5          4         --                                      3-17  40         5          3         --                                      4-2   20         5          1         --                                      4-3   20         5          4         --                                      4-4   20         5          2         --                                      4-8   20         5          3         --                                      4-9   20         5          0         --                                      4-13  20         5          2         --                                      5-3   20         5          5         5                                       5-6   20         3          5         5                                       6-1   20         5          3         --                                      6-4   20         5          4         --                                      6-6   20         5          4         --                                      6-9   20         5          2         --                                      6-11  20         5          2         --                                      ______________________________________                                    

(2) Post-emergence Test

A square pot 7.1×7.1 cm was filled with paddy field soil, submerged tothe state of a paddy field, and Echinochloa oryzicola and Monochoriavaginalis were seeded therein. Then, the seeds were allowed to germinateat room temperature for 7 days, and a predetermined amount of the testcompound in 5 ml/pot of water was applied with a pipette on the watersurface. After the treatment, management was performed in a greenhousefor 20 days, and the herbicidal effect was evaluated by observationaccording to the same standards as in Test Example 1 to obtain theresults shown in Table 10.

                  TABLE 10                                                        ______________________________________                                        Exam- Application                                                                              Herbicidal effect                                            ple   rate       Echinochloa                                                                              Monochoria                                                                              Cyperus                                 No.   (g/a)      oryzicola  vaginalis difformis                               ______________________________________                                        1-2   40         5          0         --                                      1-6   40         5          0         --                                      1-13  40         5          0         --                                      1-15  40         5          0         --                                      1-22  40         5          0         --                                      2-1   40         5          0         --                                      2-2   40         5          2         --                                      2-7   40         5          2         --                                      3-7   40         5          3         --                                      3-9   20         5          5         --                                      3-10  20         5          5         --                                      3-14  20         5          4         --                                      3-17  40         5          2         --                                      4-2   20         5          0         --                                      4-3   20         5          1         --                                      4-4   20         5          3         --                                      4-8   20         5          3         --                                      4-9   20         5          0         --                                      4-13  20         5          1         --                                      5-3   20         5          3         4                                       5-4   20         2          3         2                                       5-6   20         1          5         5                                       6-1   20         5          3         --                                      6-4   20         5          3         --                                      6-6   20         5          3         --                                      6-9   20         5          2         --                                      6-11  20         5          2         --                                      ______________________________________                                    

What is claimed is:
 1. A compound of the formula: ##STR41## wherein Q¹is N; R is H or C₁ -C₅ alkyl; X is H, halogen, CF₃, or NO₂ ; Y is H orhalogen; Z is --O--; A is ##STR42## wherein R¹² and R¹³ are each H or C₁-C₅ alkyl; R¹⁴ is C₁ -C₅ alkyl, C₂ -C₆ alkenyl, C₆ -C₁₀ aryl, or C₇ -C₁₅aralkyl; or R¹³ and R¹⁴ taken together form C₃ -C₄ alkylene; or a saltthereof.
 2. A compound as claimed in claim 1, wherein Q¹ is N; R is CH₃; X is CF₃ ; Y is H or chloro; Z is --O--; A is ##STR43## wherein R¹²and R¹³ are each H, C₁ -C₅ alkyl, R¹⁴ is C₁ -C₅ alkyl, C₂ -C₆ alkenyl,C₆ -C₁₀ C₆ -C₁₀ aryl or C₇ -C₁₅ aralkyl; R¹³ and R¹⁴ taken together formC₃ -C₄ alkylene.
 3. A herbicidal composition comprising (i) aherbicidally effective amount of a compound according to claim 1 as aneffective ingredient and (ii) a herbicidally acceptable carrier.